Experience with 20% subcutaneous immunoglobulin in the treatment of primary immunodeficiency

Primary Immunodeficiencies and Their Treatment

Congenital immune disorders, also known as primary immunodeficiencies (PIDs), arise from germline mutations affecting the functioning of the immune system. The majority of PIDs are represented by antibody production disorders. Patients with insufficient humoral immunity are highly susceptible to a range of infections, primarily bacterial. For the prevention of infections, these patients typically receive lifelong replacement therapy.

Compared to intravenous administration of immunoglobulins (IVIG), subcutaneous immunotherapy (SCIG) offers patients the option of home administration. Substitution therapy preparations are made by purifying immunoglobulins from donor plasma, and the resulting protein concentration in individual SCIG preparations ranges from 10% to 20%. A higher concentration of Ig reduces the administered volume, shortens the application time, and facilitates administration.

A study published in 2019 in the journal Immunotherapy evaluated the pharmacokinetic profile, safety, and efficacy of an innovative 20% concentration of normal human IgG (IGSC-C 20%) prepared from donor plasma using cold ethanol fractionation, caprylate precipitation, and subsequent purification via anion-exchange chromatography.

Study Methodology

The prospective multicenter open-label phase III study with a single treatment sequence was conducted between 2016 and 2017. Patients aged 2 to 72 years were administered the preparation intravenously (IGIV-C 10%) during the run-in phase for 3-4 months. This preparation was made using the same method as IGSC-C 20%, with a dose of 300–800 mg/kg administered once every 3-4 weeks. Pharmacokinetic profiling was then conducted, and the participants (n = 49) subsequently switched to subcutaneous treatment, administered once a week at a 1.37 times higher total dose than the IV preparation for 24 weeks. In week 13, pharmacokinetic profiling was repeated.

The primary objective of the study was to determine the optimal weekly dose to achieve steady-state IgG concentrations that would be noninferior to the IV preparation. Safety and tolerability of the treatment were also assessed. Exploratory objectives included the analysis of infection incidence rates.

Study Findings

Using a dose adjustment factor of 1.37, IGSC-C 20% therapy provided noninferior and bioequivalent overall IgG exposure compared to IGIV-C 10%. Additionally, subcutaneous administration resulted in higher average trough IgG concentrations and smaller fluctuations in IgG levels.

A total of 33 (62.3%) participants reported 79 adverse events (AEs; 0.303 AEs/infusion) during IV therapy, while 41 (83.7%) participants reported 141 AEs (0.134 AEs/infusion) during SC therapy. Most of these were local reactions at the administration site, with the majority (96.5%) being mild or moderate in intensity. No serious AEs potentially related to the treatment were observed.

The observed annual rate of serious bacterial infections (SBIs) during IGSC-C 20% administration was 0.049 SBI/patient-year (95% confidence interval [CI] 0.020–0.098), with one participant experiencing sepsis due to an animal bite. During IV therapy, pneumonia and sepsis were observed in one patient, corresponding to an annual SBI rate of 0.120 (95% CI 0.051–0.232).

The incidence of confirmed infections was also comparable between the two phases: 0.658/patient-year (95% CI 0.378–1.051) for intravenous treatment vs. 0.493/patient-year (95% CI 0.273–0.809) for subcutaneous therapy.

Conclusion

In the cited study, IGSC-C 20% proved comparable to IGIV-C 10%, with good tolerability and a similar safety profile.

Sources:

1. Sleasman J. W., Lumry W. R., Hussain I. et al. Immune globulin subcutaneous, human – klhw 20% for primary humoral immunodeficiency: an open-label, phase III study. Immunotherapy 2019; 11 (16): 1371–1386, doi: 10.2217/imt-2019-0159.
2. SPC Xembify. Available at: https://prehledy.sukl.cz/prehledy/v1/dokumenty/68883